This document discusses bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). It provides information on: - The normal vaginal flora being dominated by lactobacillus which prevents infection, while BV involves a shift reducing lactobacillus. - Risk factors, presentations, and treatments for BV including the role of Gardnerella vaginalis biofilms. Recurrence is common. - Commensal and pathogenic forms of Candida albicans causing VVC. Symptoms, recurrent forms, and treatment with antifungals.

1. Dr Helen Henzell
Melbourne Sexual Health Centre
October 2015

4. A lactobacillus dominated vaginal flora is inhospitable
to many bacteria, including chlamydia and gonorrhea,
and reduces susceptibility to viruses likes HIV-1 and
HSV
More than 20 species of Lactobacillus have been
detected in the vagina.
Normal vaginal flora is dominated by one or two
species of Lactobacillus, mainly L. crispatus, L. iners,
L. jensenii, or L. gasseri
Lamont. BJOG. 2011

5. Heatmap of log10-transformed proportions of microbial taxa found in the vaginal bacterial
communities of 394 women of reproductive age (color key is indicated in the lower right corner).
Jacques Ravel et al. PNAS 2011;108:4680-4687©2011 by National Academy of Sciences

6. Shift in the vaginal flora
Reduced numbers of lactobacilli and massive increase in
anaerobes with increased species diversity
Fredricks. NEJM. 2005
Most common cause of vaginal discharge in
reproductive aged women
Causes ~50% vaginal discharge in reproductive age women
Common in asymptomatic women
30% general U.S. population, 50% African American
NHANES 2007
8-16% general population Sri Lanka
Sathyadevi. Retrovirology.2012
Kenyon. Eur J Obstet Gynecol & Reprod Gynecol. 2014

7. BV presents as a
polymicrobial biofilm

8. D. Davis - From: Looking for Chinks in the Armor of Bacterial Biofilms Monroe D. PLoS Biology Vol. 5, No. 11
1. Initial attachment. 2. Irreversible attachment. 3. Maturation I. 4. Maturation II. 5. Dispersion

9. Gardnerella vaginalis is the first species to adhere
to vaginal epithelium and create a scaffolding to
which other species adhere (biofilm)
Verstraelen. Curr Opin Infect Dis 2013
Biofilms protect bacteria from host immune
response and demonstrate 10-1000 fold increase in
adaptive resistance to conventional antibiotics
Cesar de la Fuente. PLOS Pathol. 2014

10. Sexual activity Fethers. CID. 2008
Increased risk with new male partner or multiple male partners (RR 1.6), or
female partner (RR 2.0)
Smoking Bagaitker. Biomed Central. 2008
Two fold increased risk
Douching Brotman. Am J Epid. 2008
Increased risk (RR 1.21)
Condom use Hutchinson. Epidem. 2007
Reduced risk with consistent condom use (OR 0.37)
Hormonal contraception Vodstrcil. PLOS ONE. 2013
Reduced risk of BV (RR 0.78) and reduced recurrent BV (RR 0.69)

11. Gardnerella vaginalis has both adherent and
dispersed forms
Cohesive Gardnerella (clue cell) is present in all
patients with proven BV and their partners
Cohesive Gardnerella present in 7% men and 13%
women hospitalised for other reasons than BV, 16%
of pregnant women
Swidsinski. Gynecol Obstet Invest. 2010

12. Increased vulnerability to HIV and STIs
Up to 60% increased risk HIV acquisition
Increased risk HIV transmission to partners
Increased acquisition chlamydia, gonorrhea, trichomonas, herpes
Increased risk of upper genital tract infection due to
opportunistic infections
PID, upper genital tract infection following gynecological procedures and
post partum endometritis
Poor pregnancy outcomes
Two fold increased risk preterm delivery
Increased early and late miscarriage
Verstraelen. Expert Rev Anti Infect Ther. 2009

13. However the majority of women with BV do not
experience adverse outcomes
BV is not a homogeneous infection
Continuing research to determine if there are
specific organisms, or groups of organisms, that
are implicated in adverse outcomes

14. FIGURE 1. Diagnostic tests for bacterial vaginosis.
Deborah B. Nelson, and George Macones Epidemiol Rev
2002;24:102-108
©2002 by Oxford University Press

17. Nugent score

18. Other tests for BV
 Point of care (pH, sialidase activity ‘BV blue’, probe for
Gardnerella vaginalis RNA [Affirm BD diagnostic system
– also detects Trichomonas and Candida])
 Molecular – detection 16s rRNA gene
There is no ideal test
All tests have problems with sensitivity and specificity
and inter-test variability
Molecular testing will probably supersede other tests for
research but need to refine targets

19. • Metronidazole oral – 500mg twice daily x 7 days
• Metronidazole gel 0.75% - 5g intravaginally once daily for 5
days
• Clindamycin cream 2% - 5g intravaginally at bedtime for 7
days
Alternative regimens:
• Tinidazole oral 2g once daily for 2d or 1g orally for 5 days
• Clindamycin 300mg orally twice daily x 7 days or 100mg
ovules PV at bedtime for 3 days
All treatments 80-90% success rate at 1 month
Koumans. CID. 2002

20. 50% of women relapse within 12 months whatever the
regimen used
Recurrent BV defined as 3 or more episodes in a year
Reduced rates of recurrence with condom use,
abstinence, oral contraceptive pill
Sexual transmission and/or antibiotic resistant biofilms
and/or wrong antibiotic treatment?
Bradshaw. JID. 2006

21. After first line course of treatment:
• continue with 0.75% metronidazole gel PV twice
weekly for 4-6 months
OR
• Intravaginal boric acid 600mg capsules daily for 21 days
and then suppressive metronidazole gel as above
OR
• Monthly oral metronidazole 2g together with
fluconazole 150mg
High rate of relapse once stop suppression

22. • Is BV an infection?
• Is BV sexually transmitted?
• What is the ideal diagnostic test?
• Should partners be treated?
• What is the most effective treatment?
In pregnancy
• Is there a benefit to screening and treating BV in
pregnant women <20/40?
• If treatment is used in pregnancy what is the best
treatment?
Cochrane Database Syst Rev, 2015
Lamont. AJOG. 2011

23. Biofilm busters: Small molecules and enzymes
have been investigated to inhibit or disrupt
biofilm formation (Boric acid most well known)
Probiotics – lactobacilli
Treating partners

25. Opportunistic fungal pathogen that exists as a harmless
commensal in the GUT and GIT of 70% humans
As part of commensal flora, C.albicans is more frequently
isolated than other species (70% vs 7% for C. glabrata
and C. tropicalis)
Antibiotics enable C. albicans to multiply as other
commensal flora are diminished (reduced competition)
and this can result in up regulation of certain genes and
switch to opportunistic pathogen
Ahmad. Combating fungal infections. 2010

26. In commensal form C. albicans resides in yeast form
and multiplies by budding

27. When it becomes pathogenic it switches to hyphal form

28. Most symptomatic infections are caused by
C. albicans
75% of women are affected by VVC at least once
in their lifetime and 5-10% experience recurrent
infection Sobel. Lancet. 2007

29. Symptoms are due to host immune response
In susceptible women, symptomatic infection is
associated with a robust neutrophil migration
into the vagina that illicit an inflammatory
response that is not protective and is a major
cause of symptoms
Fidel. Infect Immun. 2004

30. Candida biofilms
Candida albicans form pathogenic mucosal biofilms
in the vagina Harriot. Microbiology.2010
Biofilms can be polymicrobial, and Gardnerella
vaginalis can exist with Candida species within a
biofilm
Non-albicans species also form adhesive biofilms
Silva-Dias. Front Microbiol. 2015

31. Recurrent/chronic
Acute candidiasis
Symptoms:
Discharge
Itch
Discomfort with sex
Splitting and swelling with sex
Signs:
Erythema
Characteristic discharge
Yeasts and polymorphs on
microscopy
Chronic/recurrent
Symptoms:
Dryness and poor lubrication
Irritation
Raw or burning with sex
Cyclical symptoms with premenstrual flare
Improves with antifungal treatment but
relapse
Signs:
Examination can be normal
Can have negative microscopy and culture
within 4-6 weeks of treatment

36.  ≥4 episodes in a year
 Affects 5-10% of women in reproductive years
 Host-pathogen interaction resulting in a localised hypersensitivity -
increased incidence in atopic individuals
 Can be associated with diabetes or immune suppression
 Often culture negative if recent antifungal treatment – these
women are more sensitive than culture medium
 Significant cause of vulvodynia

37. Short course vaginal treatment with any standard
imidazole agent (clotrimazole, miconazole, econazole,
terconazole cream or pessaries for 1-7 days)
OR
Oral fluconazole 150mg once in a single dose
Avoid fluconazole in pregnancy: FDA Cat C for single
dose and Cat D for repeated doses

38. Fluconazole 150mg every third day for 3 doses and
then once weekly for 6 months (30%-50% relapse
on stopping and need to continue for longer)
May need twice weekly dosing if breakthrough
symptoms (e.g. 100mg twice weekly)
Or, if oral treatment not readily available or contra-
indicated, vaginal antifungal cream or pessary twice
weekly or 500mg clotrimazole pessary once weekly
for 6 months

39. Approx. 5-10% of recurrent infection is caused by non-albicans
yeasts, the majority being C. glabrata
Non-albicans yeasts often do not cause symptoms – check for
other causes (burning or itch may be caused by contact
dermatitis or vulvodynia)
Trial of treatment is reasonable to see if it is a cause of
symptoms
Non-albicans yeasts are less responsive to standard antifungal
agents and C. krusei has innate resistance to fluconazole

40. Optimal treatment unknown
Longer duration of any standard imidazole PV treatment for 7-14 days,
or a non-fluconazole oral agent (ketoconazole or itraconazole)
If first line treatment fails:
• Boric acid 600mg gelatin capsules PV for 2 weeks (70% eradication)
• (amphotericin lozenge PV nightly for 2 weeks)
If recurrent infection:
• After induction with standard therapy continue with suppression
with any agent that works, twice weekly for 6 months (may need to
use more frequently)